MoA of antibiotics that acting on cell wall synthesis
Inhibition of cell wall synthesis -> bacteria dies
2 examples of classes of the antibiotics that act on cell wall synthesis
- Beta-lactams: Penicillins, Cephalosporins
- Glycopeptides: Bacitracin
MoA of antibiotics disturb cell membrane
Antibiotic binds to the cell membrane ->altering its structure -> cell membrane becomes more permeable -> disruption of osmotic balance -> leakage of cellular molecules -> increase water uptake -> cell death
(2) examples of classes of antimicrobials that ac by disruption of a cell membrane
Polymyxins and Polyenes (anti-fungal)
(2) examples of antibiotics that act by preventing DNA from being synthesised
Examples: Quinolines, nalidixic acid
Example of antibiotic that act by preventing of RNA being synthesised
Rifamycin
Examples of antibiotics that disturb protein synthesis by targeting 50s unit of ribosome
50s subunit: Erythromycin, Chloramphenicol
Examples of antibiotics that target protein synthesis at 30s unit of ribosome (2)
30s subunit: Tetracycline, Streptomycin
General mechanism of action of protein synthesis inhibitors
Subunit targeted by an antibiotic -> disruption of
ribosomes -> bacteria unable to make proteins
-> bacteria can stay alive but is unable to do
anything
(Therefore these antibiotics are bacteriostatic -
prevent bacterial growth)
Mechanism of action of inhibitors of folic acid metabolism
- bacteria metabolise PABA (precursor) -> foliate (folic acid)
- folic acid is essential for the synthesis of: thymine and adenine (2 out of 4 nucleic acids that make up DNA)
Antibiotics:
PABA cannot convert into folic acid -> prevent
DNA synthesis
(2) examples of antibiotics that act as folic acid inhibitors
Sulphonamides, Trimethoprim
Mechanism of action of beta-lactams
Beta-lactams = Penicillins
Mechanism of action: inhibit cell wall synthesis = bactericidal
Mechanism of resistance to beta-lactams
Mechanism of resistance: production of beta - lactamases -> hydrolysis of beta - lactam -> antibiotic structure is broken -> drug inactivation
What drugs can overcome resistance from beta-lactamases?
Co-amoxiclav and Tazocin
Can inhibit beta-lactamase so can overcome resistance -> however have little antimicrobial effect -> given in combination with amoxicillin and Pipercillin
- mixed spectrum: gram positive and gram negative
MoA of cephalosporins
Cephalosporins = beta-lactams
MoA:inhibit cell wall synthesis = bactericidal
MoA of Carbapenems
Carbopenems= beta-lactams
Mechanism of action: inhibit cell wall synthesis = bactericidal (like all beta-lactams)
Binding to penicillin-binding proteins -> inhibition of cell wall synthesis
Use of carbapenems
- most stable beta-lactam -> broader spectrum of activity than penicillins and cephalosporins
- broad spectrum (action against gram positive and gram negative organisms)
- used against multi-drug resistant bacteria:
- does not work against: MRSA, Enterococci and Pseudomonas)
- last line of defence
- used in hospitalised patients
Example of antibiotics (2) that belong to glycopeptides class
Vancomycin (used for MRSA) and Teicoplanin
Use of glycopeptides antibiotics
- used only for gram positive bacteria
- very toxic -> used as last line of defence (for patients critically ill or those with beta-lactam allergies)
- narrow spectrum of action
- bacterocidal only against enterococci
- do not penetrate to CSF
- usually given by IV
MoA of glycopeptides antibiotic
Glycopeptides e.g. Vancomycin, Teicoplanin
Mechanism: bind to amino-acid within the cell wall* -> preventing the addition of new peptidoglycan units
-> inhibition of peptidoglycan synthesis -> inhibition of cell wall synthesis
Side effects (3) of Vancomycin use
- Red Man Syndrome - appears within 4 - 10 mins after administration of IV or after completion of infusion. Flushing, erythematous rash affecting face, neck and upper torso (as vancomycin mediate Ig- independent mast cell degranulation); Rx with antihistamines; symptoms less likely to occur with slow infusion (over at least 60 minutes)
- Ototoxicity (rare)
- Nephrotoxicity
MoA of Aminoglycosides
Mechanism: act on 30s ribosomal unit -> block the initiation of translation -> misreading of mRNA
Examples: Gentamicin, Amikacin, Neomycin, Tobramycin
Examples (4) of aminoglycosides
Examples: Gentamicin, Amikacin, Neomycin, Tobramycin
Aminoglycosides
- use
- side effects
Examples: Gentamicin, Amikacin, Neomycin, Tobramycin
- Effective against: gram -ve (except Streptococci and enterococci) and gram +ve
- Side effects: Nephrotoxicity, Othotoxicity
